N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline studies on the role of 5-HT1A and 5-HT2 receptors in mediating foot-shock-induced ultrasonic vocalisation in adult rats.

The role of 5-HT1A and 5-HT2 receptors in mediating foot-shock-induced ultrasonic vocalisation has been studied in rats. Furthermore, behavioural effects were correlated to receptor reserves in the brain by means of receptor inactivation with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The dose-dependent inhibition of ultrasonic vocalisation by the 5-HT precursor, L-5-hydroxy-L-tryptophan (110-450 micromol/kg), was abolished by pretreatment with the 5-HT1A/1B antagonist, (-)-penbutolol (27 micromol/kg), and the 5-HT2A/2C antagonist, ritanserin (10 micromol/kg). The inhibitory actions of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT2A/5-HT2C. agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were reversed by the 5-HT1A antagonist, (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY-100635), and the 5-HT2A antagonist, (+/-)alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorphenyl)ethyl]-4-pipe ridine-methanol (MDL 100151), respectively. Pretreatment with EEDQ (24 h, subcutaneous [s.c.]) inhibited foot-shock-induced ultrasonic vocalisation (effective dose50=0.95 micromol/kg) and decreased [3H]-8-OH-DPAT and [3H]-ketanserin binding in the brain. Pretreatment with WAY-100635 (0.3-20 micromol/kg) 20 min prior to EEDQ administration (1.3 micromol/kg, s.c.) did not reverse the EEDQ-induced inhibition of ultrasonic vocalisation but protected the 5-HT1A receptors against EEDQ inactivation. Pretreatment with MDL 100151 (0.83-54 micromol/kg) 20 min prior to EEDQ administration both reversed the EEDQ-induced inhibition of ultrasonic vocalisation and protected the 5-HT2A receptors against EEDQ inactivation. These findings demonstrate that 5-HT1A and 5-HT2 receptors are involved in the regulation of ultrasonic vocalisation in rats. However, the function of 5-HT1A and 5-HT2 receptors in this model seems to differ as vocalisation was preserved after protection of 5-HT2 but not 5-HT1A receptors.